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Objectives <p>To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized <sup>129</sup>Xe MRI measures.</p> Materials and methods <p>Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5 ± 7.7 years; 17 men); 30 completed the MRI extension at 1.5 T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman’s rank and bootstrap 95% confidence intervals (95% CIs).</p> Results <p>PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (<i>p</i> &lt; 0.05). PWV decreased after multiple doses (−0.87 m/s, 95% CI: −1.26 to −0.48 m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and <sup>129</sup>Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (<i>ρ</i> = 0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and ¹²⁹Xe-derived VDP, apparent diffusion coefficient, and compartment ratios.</p> Conclusion <p>PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation.</p> Key Points <p><Emphasis Type="BoldItalic">Question</Emphasis> <i>Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients?</i></p> <p><Emphasis Type="BoldItalic">Findings</Emphasis> <i>Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing.</i></p> <p><Emphasis Type="BoldItalic">Clinical relevance</Emphasis> <i>PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized ¹²⁹Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.</i></p> Graphical Abstract <p></p>

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Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial

  • 期刊论文

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  • 发表日期：

    2026年5月20日

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  • Andreas Voskrebenzev,
  • Till F. Kaireit,
  • Marius M. Klein,
  • Agilo L. Kern,
  • Lea Behrendt,
  • Filip Klimeš,
  • Robin A. Müller,
  • Thomas Kayser,
  • Frank Wacker,
  • Jens Vogel-Claussen,
  • Jens M. Hohlfeld

摘要

Objectives

To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129Xe MRI measures.

Materials and methods

Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5 ± 7.7 years; 17 men); 30 completed the MRI extension at 1.5 T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman’s rank and bootstrap 95% confidence intervals (95% CIs).

Results

PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (p < 0.05). PWV decreased after multiple doses (−0.87 m/s, 95% CI: −1.26 to −0.48 m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and 129Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (ρ = 0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and ¹²⁹Xe-derived VDP, apparent diffusion coefficient, and compartment ratios.

Conclusion

PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation.

Key Points

Question Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients?

Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing.

Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized ¹²⁹Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.

Graphical Abstract